Sinha Arjun, Zheng Yinan, Nannini Drew, Qu Yishu, Hou Lifang, Shah Sanjiv J, Yancy Clyde W, McNally Elizabeth M, Fornage Myriam, Lima Joao, Lloyd-Jones Donald M, Rasmussen-Torvik Laura J, Khan Sadiya S
Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
JAMA Cardiol. 2021 Jun 1;6(6):718-722. doi: 10.1001/jamacardio.2020.6623.
The variant V122I is commonly enriched in the transthyretin (TTR) gene in individuals of African ancestry and associated with greater risk of heart failure (HF) in older adulthood, after age 65 years. Prevention of HF may be most effective earlier in life, but whether screening with echocardiography can identify subclinical cardiac abnormalities during middle age to risk-stratify individuals appears to be unknown.
To examine the association between the V122I TTR variant and cardiac structure and function during middle age in those without prevalent HF.
DESIGN, SETTING, AND PARTICIPANTS: This serial cross-sectional study of 875 Black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort was conducted at 4 urban sites across the US. Recruiting was completed in 1985-1986, and follow-up examinations occurred 25 and 30 years later. A subset of Black adults from the CARDIA cohort who underwent TTR genotyping was included. Data analysis was completed from January 2020 to October 2020.
The V122I TTR genotype.
Echocardiographic left ventricular (LV) circumferential and longitudinal systolic strain and LV structure, measured at years 25 and 30 of follow-up. The analyses were adjusted for age, sex, echocardiography quality, genetic ancestry, and field center.
Among the 875 Black adults (mean [SD] age, 49.4 [3.8] years at year 25; 543 women [62.1%]), there were 31 individuals who were heterozygous and 1 who was homozygous for the V122I TTR variant. Of the adults who had an echocardiogram at year 25, rates of hypertension (312 [46%]), diabetes (102 [15%]), and current smoking (128 [19%]) were not significantly different between those who did and did not carry V122I TTR. At year 25, there was no difference in LV circumferential strain, longitudinal strain, or LV structure between those who did vs did not carry V122I TTR. At year 30, those who carried V122I TTR had significantly lower absolute LV circumferential strain (mean [SD], 12.4 [4.2] percentage units) compared with those who did not carry the variant (mean [SD], 14.5 [3.7] percentage units). Those who carried V122I TTR also had significantly higher LV mass index values (mean [SD], 97.5 [34.1] g/m2) compared with those who did not (mean [SD], 83.7 [22.6] g/m2) at year 30.
Carrier status for the V122I TTR variant is associated with subclinical cardiac abnormalities in middle age (worse LV systolic function and higher LV mass) that have been associated with increased risk of incident HF. Midlife screening of individuals who carry V122I TTR with echocardiography may prognosticate risk of symptomatic HF and inform prevention strategies.
V122I变异在非洲裔个体的转甲状腺素蛋白（TTR）基因中普遍富集，与65岁及以上老年人心力衰竭（HF）风险增加相关。HF的预防可能在生命早期最为有效，但超声心动图筛查能否在中年时识别亚临床心脏异常以对个体进行风险分层似乎尚不清楚。
研究无HF病史的中年人群中V122I TTR变异与心脏结构和功能之间的关联。
设计、地点和参与者：这项对875名参加青年成人冠状动脉风险发展研究（CARDIA）队列的黑人参与者进行的系列横断面研究在美国4个城市地点开展。招募于1985 - 1986年完成，25年和30年后进行随访检查。纳入了CARDIA队列中接受TTR基因分型的一部分黑人成年人。数据分析于2020年1月至2020年10月完成。
V122I TTR基因型。
在随访的第25年和第30年测量的超声心动图左心室（LV）圆周和纵向收缩应变以及LV结构。分析针对年龄、性别、超声心动图质量、遗传血统和研究中心进行了校正。
在875名黑人成年人中（第25年时平均[标准差]年龄为49.4[3.8]岁；543名女性[62.1%]），有31人为V122I TTR变异的杂合子，1人为纯合子。在第25年进行超声心动图检查的成年人中，携带和未携带V122I TTR的人群中高血压（312[46%]）、糖尿病（102[15%]）和当前吸烟（128[19%]）的发生率无显著差异。在第25年，携带和未携带V122I TTR的人群在LV圆周应变、纵向应变或LV结构方面无差异。在第30年，携带V122I TTR的人群与未携带该变异的人群相比，绝对LV圆周应变显著更低（平均[标准差]，12.4[4.2]个百分点）。在第30年，携带V122I TTR的人群与未携带该变异的人群相比，LV质量指数值也显著更高（平均[标准差]，97.5[34.1]g/m²）。
V122I TTR变异的携带状态与中年时的亚临床心脏异常相关（LV收缩功能较差和LV质量较高），这些异常与HF发病风险增加有关。对携带V122I TTR的个体进行中年超声心动图筛查可能有助于预测有症状HF的风险并为预防策略提供依据。
